Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome

Abstract

IMPORTANCEClopidogrel monotherapy after short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has not yet been fully investigated in patients with acute coronary syndrome (ACS).OBJECTIVE To test the hypothesis of noninferiority of 1 to 2 months of DAPT compared with 12 months of DAPT for a composite end point of cardiovascular and bleeding events in patients with ACS. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, open-label, randomized clinical trial enrolled 4169 patients with ACS who underwent successful PCI using cobalt-chromium everolimus-eluting stents at 96 centers in Japan from December 2015 through June 2020. These data were analyzed from June to July 2021.INTERVENTIONS Patients were randomized either to 1 to 2 months of DAPT followed by clopidogrel monotherapy (n = 2078) or to 12 months of DAPT with aspirin and clopidogrel (n = 2091). MAIN OUTCOMES AND MEASURESThe primary end point was a composite of cardiovascular (cardiovascular death, myocardial infarction [MI], any stroke, or definite stent thrombosis) or bleeding (Thrombolysis in MI major or minor bleeding) events at 12 months, with a noninferiority margin of 50% on the hazard ratio (HR) scale. The major secondary end points were cardiovascular and bleeding components of the primary end point. RESULTS Among 4169 randomized patients, 33 withdrew consent. Of the 4136 included patients, the mean (SD) age was 66.8 (11.9) years, and 856 (21%) were women, 2324 (56%) had ST-segment elevation MI, and 826 (20%) had non-ST-segment elevation MI. A total of 4107 patients (99.3%) completed the 1-year follow-up in June 2021. One to 2 months of DAPT was not noninferior to 12 months of DAPT for the primary end point, which occurred in 65 of 2058 patients (3.2%) in the 1-to 2-month DAPT group and in 58 of 2057 patients (2.8%) in the 12-month DAPT group (absolute difference, 0.37% [95% CI, −0.68% to 1.42%]; HR, 1.14 [95% CI, 0.80-1.62]; P for noninferiority = .06). The major secondary cardiovascular end point occurred in 56 patients (2.8%) in the 1-to 2-month DAPT group and in 38 patients (1.9%) in the 12-month DAPT group (absolute difference, 0.90% [95% CI, −0.02% to 1.82%]; HR, 1.50 [95% CI, 0.99-2.26]). The major secondary bleeding end point occurred in 11 patients (0.5%) in the 1to 2-month DAPT group and 24 patients (1.2%) in the 12-month DAPT group (absolute difference, −0.63% [95% CI, −1.20% to −0.06%]; HR, 0.46 [95% CI, 0.23-0.94]). CONCLUSIONS AND RELEVANCEIn patients with ACS with successful PCI, clopidogrel monotherapy after 1 to 2 months of DAPT failed to attest noninferiority to standard 12 months of DAPT for the net clinical benefit with a numerical increase in cardiovascular events despite reduction in bleeding events. The directionally different efficacy and safety outcomes indicate the need for further clinical trials.

EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer

“… b The 2020 ESC guidelines definition of complex coronary includes but is not limited to the following: coronary stenosis which only can be solved with bifurcation stenting with 2 stents, with very long and small stents, with >3 stents, with >3 stented lesions. 165 ACS = acute coronary syndrome; STEM = ST elevation MI. …”

“…Recent noninferiority studies have shown that de-escalation to SAPT after a DAPT duration of only 3 months with clopidogrel post-PCI for ACS and after 1 month post-PCI for stable chronic coronary syndrome, is safe, particularly in vulnerable patient groups. 140 , 165 – 167 This strategy may also be adopted in patients with TP, in whom the indication for DAPT should be re-evaluated when TP occurs as well. Thus, in the context of TP, one should consider the relatively lower bleeding risk associated with DAPT with clopidogrel as compared to DAPT with ticagrelor or prasugrel.…”

Still a Long Way to the Precision Medicine of Antiplatelet Strategy After Percutaneous Coronary Intervention

“…In addition, there is an unmet need for revealing the optimal intensity of P2Y 12 inhibitor monotherapy following dropping aspirin. In the STOPDAPT-2 ACS trial (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 in Patient With Acute Coronary Syndrome) 10 enrolling Japanese ACS patients (n=4136), short-term DAPT strategy (clopidogrel monotherapy following 1-month DAPT) was associated with the increased risk of myocardial infarction (1.59% versus 0.85%) and a numerical increase of stent thrombosis (0.45% versus 0.20%), albeit at the benefit of a lower incidence of Bleeding Academic Research Consortium 3 or 5 bleeding (0.54% versus 1.31%) compared with the 12-month DAPT strategy. Aspirin discontinuation with clopidogrel monotherapy in the early phase (within 1 month) may increase the risk of ischemic events even in ACS patients with low thrombotic risk (eg, East Asian patients).…”

Prescribing aspirin to older people – where is the line between cardiovascular benefit and upper gastrointestinal bleeding risk?

“…13 In contrast, a trial testing a similar concept using clopidogrel instead of ticagrelor after an acute coronary event reported a less favourable ischaemic risk in the clopidogrel monotherapy arm. 14 Whether and how to apply the accumulating data using abbreviated or de-escalated antiplatelet therapy after revascularisation or acute coronary events is a complex decision that requires an in-depth understanding of the different study designs, study populations, antiplatelet agents and the specific ischaemic and bleeding risk of the patient, as was recently shown. 15 A trial specifically targeting patients at high risk of bleeding reported that, following percutaneous coronary revascularisation, the discontinuation of aspirin after 1 month reduced the risk of actionable bleeding with a neutral effect on ischaemic events when compared to the continuation of dual antiplatelet therapy for 12 months.…”

“…A blinded trial of 7119 patients who were randomised after receiving dual antiplatelet therapy for 3 months following revascularisation reported lower bleeding and non‐inferior ischaemic risk reduction in the intervention arm treated with ticagrelor monotherapy when compared to the control group of ticagrelor plus aspirin for the remaining 12 months 13 . In contrast, a trial testing a similar concept using clopidogrel instead of ticagrelor after an acute coronary event reported a less favourable ischaemic risk in the clopidogrel monotherapy arm 14 . Whether and how to apply the accumulating data using abbreviated or de‐escalated antiplatelet therapy after revascularisation or acute coronary events is a complex decision that requires an in‐depth understanding of the different study designs, study populations, antiplatelet agents and the specific ischaemic and bleeding risk of the patient, as was recently shown 15 .…”